scholarly journals Post-Transplant CD34+ Selected Stem Cell “Boost” as Intervention for Mixed Chimerism Following Reduced Intensity Conditioning HSCT in Children and Young Adults with Primary Immune Deficiencies

2018 ◽  
Vol 24 (3) ◽  
pp. S433-S434
Author(s):  
Sharat Chandra ◽  
Jack J. Bleesing ◽  
Michael B. Jordan ◽  
Michael S. Grimley ◽  
Pooja Khandelwal ◽  
...  
Keyword(s):  
Young Adults ◽  
Stem Cell ◽  
Mixed Chimerism ◽  
Reduced Intensity Conditioning ◽  
Post Transplant ◽  
Immune Deficiencies ◽  
Children And Young Adults ◽  
Reduced Intensity

High Rates of Early Donor Chimerism and Low Risk of Chronic GVHD Can Be Achieved in Poor Risk Patients Undergoing Unrelated Donor Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen Incorporating Fludarabine, Busulfan, and Rabbit ATG.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5080-5080
Author(s):  
Mehdi Hamadani ◽  
Patrick Elder ◽  
Farrukh Awan ◽  
David Krugh ◽  
William Blum ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Post Transplant ◽  
Ebv Reactivation ◽  
Risk Patients ◽  
Reduced Intensity

Abstract Reduced intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT) in patient groups with relative contraindications for transplantation since they promote effective engraftment of donor cells with minimal regimen related toxicity. However, following unrelated donor (URD) transplantation, high rates of acute and extensive chronic GVHD have mitigated the overall benefits of this approach. We pursued a strategy designed to enhance early full donor hematopoietic chimerism while potentially reducing the risk of severe acute and extensive chronic GVHD using an RIC regimen containing fludarabine (F), busulfan (B), rabbit antithymocyte globulin (A) (FBA) followed by URD SCT in 30 consecutive high risk patients (pts). Criteria for selection included advanced age (>55yrs), prior autograft, and/or high co-morbidity index (median 2, range 0–4). There were 24 male and 6 female pts with a median age of 53 years (range 22–66yrs). Diagnoses included AML (N=10), NHL (N=7), Hodgkin’s lymphoma (N=6), advanced CML (N=4), and advanced CLL (N=4). Nine pts had previously undergone autologous SCT. 43% had a Karnofsky performance status of 70 or 80% at the time of transplant. 80% were matched with their donor at HLA-A, B, C, and DRB1 by high-resolution DNA typing, while 3 were mismatched at 1 antigen and 3 mismatched at 1 or 2 alleles. All pts were conditioned with F (30 mg/m2/day, days −7 to −3), B (0.8 mg/kg/dose IV x 8 doses) and A (2.5 mg/kg/day, days −4 to −2) followed by micro-dose methotrexate and tacrolimus. Stem cell source included peripheral blood (n=26) or bone marrow (n=4). All pts engrafted neutrophils and platelets promptly (median 15 and 16 days, respectively). There were no primary graft failures. Rates of grade II-IV and III-IV acute GVHD were 43% (n=13) and 23% (n=7) respectively. Nine pts (30%) developed chronic GVHD but extensive chronic GVHD was seen in only 10% (n=3). Day 100 TRM was 10% (n=3). Causes of death included disease progression=2, post-transplant lymphoproliferative disorder (PTLD) =1 and sepsis=1. CMV and EBV reactivation occurred in 30% (n=9) and 20% (n=6) respectively. 2 pts developed PTLD requiring rituximab. Three pts had BK-virus associated hemorrhagic cystitis. Lineage-specific chimerism analysis showed 100% donor CD33+ at all time points (days 30, 60, 100) and median donor CD3+ chimerism of 94% at day +30 and 100% at day +100. One patient had secondary graft failure. 23 pts (76%) were in CR after SCT. The median follow-up of surviving patients is 6 months (range 1–32 months). Kaplan-Meier estimates of overall survival (OS) and progression free survival (PFS) at 1year are 62% and 43% respectively. Using the Log-Rank test, OS (P=0.95) and PFS (P=0.65) was not statistically significant between recipients of matched and mismatched grafts. In conclusion, this approach using FBA and a tacrolimus based GVHD prophylaxis achieved rapid donor chimerism and a favorably low incidence of TRM, acute, and chronic GVHD despite being tested in a poor risk group of pts. Although rates of infectious complications were within expected ranges, the rate of both EBV reactivation and disease relapse warrant further exploration of this approach using lower doses of ATG (e.g. 5–6mg/kg total dose) combined with post transplant immunomodulation.

Outcome of Sibling Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantations in Low-Grade B Cell Lymphoproliferative Disorders. A Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5059-5059
Author(s):  
Ronan Desmond ◽  
Marianna David ◽  
Eibhlin Conneally ◽  
Paul Browne ◽  
Mairead Ni Conghaile ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Lymphoproliferative Disorders ◽  
Mixed Chimerism ◽  
Low Grade ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity

Abstract Reduced intensity conditioning allogeneic stem cell transplantations (allo-SCT) have been developed to exploit graft-versus-malignancy effect while reducing the toxicity of allo-SCT. We report the outcome of 21 patients with low-grade B cell lymphoproliferative disorders transplanted in a single center. The mean age of the patients was 54 years (range 32–66) with 11 males, 10 females. Follicular lymphoma was the diagnosis in 10 patients, CLL in 5, mantle cell lymphoma in 4, MALT lymphoma in 1 and lymphoplasmocytoid lymphoma in 1 patient. The median number of prior treatment lines was 2. All patients received peripheral blood stem cell transplants from sibling donors and no patients had undergone a prior autologous SCT. 12/21 patients (57%) received a ATG based conditioning regimen while the remainder, 9/21 (42%) received a Campath containing conditioning regimen. Full donor chimerism was confirmed in 17/19 (89%) patients. Acute graft versus host disease (GVHD) developed in 5/21 (23%) of the patients. Chronic GVHD occurred in 7/21 (33%) with 5/21 occuring post donor lymphocyte infusion (DLI). DLI has been administered in 11/21 patients (52%), 2 for progressive disease and 9 for re-emerging mixed chimerism. Non-relapse mortality (NRM) at 100 days and 1 year were 5% and 12.5% respectively. With a median follow up of 21 months (range 3–54) the overall survival rates (OS) at 1 year and 2 years were 72% and 58% respectively. Progression free survival (PFS) at 1 year and 2 years were 66% and 50%. We have shown that reduced intensity conditioning allogeneic stem cell transplantation is associated with a low TRM comparible to that of autologous transplantation and allows long term control of low grade B-cell lymphoproliferative disorders.

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